Application | Comment | Organism |
---|---|---|
medicine | therapeutic potential of TBRI inhibitors in myelodysplastic syndrome, MDS. The myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by cytologic dysplasia and ineffective hematopoiesis | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
LY-2157299 | LY-2157299 inhibits TGF-beta mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells. In vivo administration of LY-2157299 ameliorates anemia in a TGF-beta overexpressing transgenic mouse model of bone marrow failure. Treatment with LY-2157199 stimulates hematopoiesis from primary myelodysplastic syndrome bone marrow specimens | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P36897 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
bone marrow | - |
Homo sapiens | - |
HS-5 cell | - |
Homo sapiens | - |
K-562 cell | - |
Homo sapiens | - |
Synonyms | Comment | Organism |
---|---|---|
alk5 kinase | - |
Homo sapiens |
TBRI | - |
Homo sapiens |
TBRI kinase | - |
Homo sapiens |
TGF-beta receptor I kinase | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | reduction in SMAD7 can lead to increased sensitivity to suppressive effects of TGF-beta on hematopoiesis. SMAD7, a negative regulator of TGF-beta receptor I (TBRI) kinase is markedly decreased in a large meta-analysis of gene expression studies from myelodysplastic syndrome marrow derived CD34+ cells, SMAD7 protein is also significantly decreased in myelodysplastic syndrome marrow progenitors. The increased TGF-beta signaling due to SMAD7 reduction can be effectively inhibited by TBRI (ALK5 kinase) inhibitor LY-2157299 | Homo sapiens |
physiological function | SMAD7 is a negative regulator of TGF-beta receptor I (TBRI) kinase. The enzyme increases Smad7 via increased TGF-beta signaling | Homo sapiens |